Cyclic AMP inhibits synthesis of prostaglandin endoperoxide (PGG 2) in human platelets

Dibutyryl-cAMP but not dibutyryl-cGMP inhibited platelet aggregation and release of 14C-serotonin and ADP when induced by collagen and arachidonate but not when induced by the endoperoxide PGG 2 * (TXB 2) induced by addition of collagen to platelet rich plasma (PRP) was decreased by dibutyryl-cAMP and agents known to increase the concentration of cAMP (PGE 1, PGD 2, theophylline and acetyl choline). PGE 2 in concentrations known to decrease cAMP levels increased the formation of TXB 2 whereas concentrations of PGE 2 known to increase cAMP levels decreased the amount of TXB 2 formed. That this was due to an effect on the cyclooxygenase was indicated by inhibition of the transformation of arachidonic acid by DB-cAMP and by high concentrations of PGE 2. Additional support for regulation of the cyclo-oxygenase by cAMP and its relevance to platelet aggregation was obtained by demonstrating stimulation of PGG 2 induced aggregation by low concentrations of PGE 2 and the absence of this effect in the presence of a cyclo-oxygenase inhibitor.